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The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats

Year 2022, Volume: 39 Issue: 4, 1150 - 1156, 29.10.2022

Abstract

This work investigated the effects of methanolic plant extract on the cardiovascular system of induced preeclamptic Wistar rats. Preeclampsia is associated with increase in high blood pressure and proteinuria. Studies have shown the only medically acceptable treatment is the removal of the fetus from the mother, however there is considerable lack of studies done to show the use of herbal medicine in the treatment and management of preeclampsia. This study reveals the use of plant extract and its effect on cardiovascular system. Three plants extract; Jatropha curcas, Alchornea cordifolia andSecamone afzelii were used for the study. Results showed that there were no observable lesion or abnormally in the cardiovascular system and the use of all three plant extracts significantly reduced blood pressure and proteinuria, thus indicating a reduction of preeclampsia from severe to mild.

References

  • Adinma, E. D. 2013. Maternal and perinatal outcome of eclampsia in tertiary health institution in Southeast Nigeria.JMatern Fetal. 26(2):211-4. doi: 10.3109/14767058.2012.722708
  • Ahmed, M., Hwang, J. H., Hasan, M. A., and Han, D. 2018a. Herbal medicine use by pregnant women in Bangladesh: a cross-sectional study. BMC Complement.Altern.Med. 18 (1), 333.doi: 10.1186/s12906-018-2399-y
  • Ahmed, S. M., Nordeng, H., Sundby, J., Aragaw, Y. A., and de Boer, H. J. 2018b.The use of medicinal plants by pregnant women in Africa: A systematic review. J. Ethnopharmacol. 224, 297–313. doi: 10.1016/j.jep.2018.05.032
  • Akbari,S., Khodadadi, B., Ahmadi, S.A.Y., Abbaszadeh, S., Shahsavar,F. Association of VitaminDLeveland Vitamin D Deficiency with Risk of Preeclampsia: A Systematic Review and Updated Meta-Analysis. Taiwan. J. Obstet. Gynecol. 2018, 57, 241–247.
  • Ali, A.M., Alobaid, A., Malhis, T.N., Khattab, A.F. 2019. Effect of Vitamin D3 Supplementation in Pregnancy on Risk of Pre-Eclampsia—Randomized Controlled Trial. Clin.Nutr. 38, 557–563.
  • Al-Ramahi, R., Jaradat, N., and Adawi, D. 2013.Use of herbal medicines during pregnancy in a group of Palestinian women. J. Ethnopharmacol. 150 (1), 79–84. doi: 10.1016/j.jep.2013.07.041
  • Arain, N., Mirza, W.A., Aslam, M. 2015. Review-Vitamin D and the Prevention of Preeclampsia: A Systematic Review. Pak. J. Pharm. Sci. , 28, 1015–1021. [PubM
  • Asuk, A.A and Willie, A. J. (2015. The phytochemical, proximate and mineral compositions of the leaf, stem bark and root of Jatropha curcas. https://doi.org/10.1016/j.apjtb.
  • Cesario, A. 1993. Screening of plants used in Argentine folk medicine for antimicrobial activity. Journal of Ethnopharamacology 139:119-128.
  • Chuang, C. H., Chang, P. J., Hsieh, W. S., Tsai, Y. J., Lin, S. J., and Chen, P. C. (2009. Chinese herbal medicine use in Taiwan during pregnancy and the postpartum period: a population-based cohort study. Int. J. Nurs. Stud. 46 (6), 787–795. doi: 10.1016/j.ijnurstu.2008.12.015
  • Duke, J. and Vasquez, R. 1994. Amazonian Ethnobotanical Dictionary, Florida, CRC Press Incorporated. 122:101-102
  • Eliakim-Ikechukwu, C. F. and Riman, E. B. 2009. The effect of aqueous ethanolic extract of Alchornea cordifolia leaf on the histology of the aorta of Wister rats. Niger J PhysiolSci
  • Felman, A. (2017. Everything you need to know about preeclampsia. Medical news. Feng, M.and DiPetrillo, K. 2009. Non-invasive Blood Pressure Measurement in Mice. Cardiovascular Genomics, 45–55. doi:10.1007/978-1-60761-247-6_3
  • Gharoro, E. P. and Igbafe, A. A. 2000.Pattern of drug useamong antenatal patients in Benin City, Nigeria. Med Sci. Monit. 6(1): 84 - 87.
  • Houghton, P. J., Hylands, P. J., Mensah, A. Y., Hensel, A., and Deters, A. M. 2005. In vitro tests and ethnopharmacological investigations: wound healing as an example,” Journal of Ethnopharmacology, 100(1-2): 100–107.
  • Houghton, P. J., Woldemaraim, T. Z., O’Shea, S. andThyagarajan, S. P. 1996.Two securinega- type alkaloids from phyllanthusamarus.Phytochemistry; 43:715-717
  • Hwang, J. H., Kim, Y.-R., Ahmed, M., Choi, S., Al-Hammadi, N. Q., Widad, N. M.,et al. 2016. Use of complementary and alternative medicine in pregnancy: across-sectional survey on Iraqi women. BMC Complementary Altern.Med. 16,191–191.doi: 10.1186/s12906-016-1167-0
  • Illamola, S. M., Amaeze, O. U., Krepkova, L. V., Birnbaum, A. K., Karanam, A., Job, K. M., et al. 2020. Use of Herbal Medicine by Pregnant Women: WhatPhysicians Need to Know. Front. Pharmacol. 10, 1483–1483. doi: 10.3389/fphar.2019.01483
  • Kafaru, E. 1994. Immense help from nature’s workshop. Nigeria, Elikat Health services Limited. P. 32.
  • Kennedy, D. A., Lupattelli, A., Koren, G., and Nordeng, H. 2013.Herbalmedicine use in pregnancy: results of a multinational study. BMC Complement.Altern.Med. 13, 355.doi: 10.1186/1472-6882-13-355
  • Khadivzadeh, T., and Ghabel, M. 2012.Complementary and alternative medicine use in pregnancy in Mashhad, Iran 2007-8.Iran J. Nurs. Midwifery Res. 17 (4), 263–269.
  • Laelago, T. 2018. “Herbal Medicine Use during Pregnancy: Benefits and Untoward Effects,” in Herbal Medicine. Ed. P. Builders. London: IntechOpen.
  • Mensah, A. Y., Houghton, P. J., Akyirem, G. N. A. et al. 2004. Evaluation of the antioxidant and free radical scavenging properties of Secamone afzelii Rhoem,” Phytotherapy Research, 18(12): 1031-1032, 2004.
  • Mirzakhani, H., Litonjua, A.A., McElrath, T.F., O’Connor, G., Lee-Parritz, A., Iverson, R., Macones, G., Strunk, R.C., Bacharier, L.B., Zeiger, R., et al 2016. Early Pregnancy Vitamin D Status and Risk of Preeclampsia. J. Clin. Investig., 126, 4702–4715.
  • Mol, B.W.J., Roberts, C.T., Thangaratinam, S., Magee, L.A., de Groot, C.J.M., Hofmeyr, G.J. Pre-Eclampsia.Lancet 2016, 387, 999–1011.J. Clin. Med. 2019, 8, 1625 15 of 22
  • Molh, A. K., Ting, L. C., Khan, J., Al-Jashamy, K., Jaafar, H., and Islam, M. N. (2008.Histopathological studies of cardiac lesions after an acute high dose administration of methamphetamine. The Malaysian journal of medical sciences : MJMS, 15(1), 23–30.
  • Nassar, N., Halligan, G.H., Roberts, C.L., Morris, J.M., Ashton, A.W. Systematic Review of First-Trimester VitaminDNormativeLevelsandOutcomesofPregnancy. Am. J.Obstet. Gynecol. 2011,205,e1–e7. [CrossRef] 40. Roth, D.E., Leung, M., Mesfin, E., Qamar, H., Watterworth, J., Papp, E. Vitamin D Supplementation during Pregnancy: State of the Evidence from a Systematic Review of Randomised Trials. BMJ 2017, 35, j5237.
  • Olaleye, M. T., Adegboye, O. O. and Akindahunsi, A. A. 2006.Alchornea cordifoli extract protects Wistar albino rats against acetaminophen-induced liver damage. Afr J Biotech. 5:2439-45
  • Orief, Y. I., Farghaly, N. F., and Ibrahim, M. I. A. 2014.Use of herbal medicines among pregnant women attending family health centers in Alexandria. Middle East Fertility Soc. J. 19 (1), 42–50. doi: 10.1016/j.mefs.2012.02.007
  • Pereira-Junior, P.P., Marocolo, M., Rodrigues, F.P., Medei, M. and Nascimento, J.H.M. 2010. Noninvasive method for electrocardiogram recording in conscious rats: feasibility for heart rate variability analysis. Anais da Academia Brasileira de Ciências 82(2): 431-437
  • Purswani, J.M., Gala, P., Dwarkanath, P., Larkin, H.M., Kurpad, A., Mehta, S. 2017. The Role of Vitamin D in Pre-Eclampsia: A Systematic Review. BMC Pregnancy Childbirth . 17, 231.
  • Rodríguez-García, C., Sanchez-Quesada, C., and Gaforio, J. 2019. Naturally lignin rich food: a dietary tool for health promotion.
  • Saccone, G., Sarno, L., Roman, A., Donadono, V., Maruotti, G.M., Martinelli, P. 2016. 5-Methyl-Tetrahydrofolate in Prevention of Recurrent Preeclampsia. J. Matern. Neonatal Med., 29, 916–920.
  • Segura-Campos, M. R., Peralta-González, F., Castellanos-Ruelas, A., Chel-Guerrero, L. A., andBetancur-Ancona, D. A. 2013. Effect of Jatropha curcas peptide fractions on the angiotensin I-converting enzyme inhibitory activity. BioMed research international, 2013, 541947. https://doi.org/10.1155/2013/541947
  • Sofowora, E. A. 1982. Medicinal plants and traditional medicine in Africa. John Wiley and sons Ltd., Hoboken, 64
  • Stefańska, K., Zieliński, M., Zamkowska, D., Adamski, P., Jassem-Bobowicz, J., Piekarska, K., Jankowiak, M., Leszczyńska, K., Świątkowska-Stodulska, R., Preis, K., Trzonkowski, P., andMarek-Trzonkowska, N. 2020. Comparisons of Dipstick Test, Urine Protein-to-Creatine Ratio, and Total Protein Measurement for the Diagnosis of Preeclampsia. International journal of environmental research and public health, 17(12), 4195. https://doi.org/10.3390/ijerph17124195
  • Ugbogu, O.A. and Chukwuma, E.C. 2019.Ethnobotany of Okomu Forest Reserve, Edo State, Nigeria. J. Appl. Sci. Environ. Manage., 23 (7): 1391-1401
  • Wei, S.-Q., Qi, H.-P., Luo, Z.-C., Fraser, W.D. 2013 Maternal Vitamin D Status and Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis. J. Matern. Fetal. Neonatal Med., 26, 889–899.
  • Wen, S.W., White, R.R., Rybak, N., Gaudet, L.M., Robson, S., Hague, W., Simms-Stewart, D., Carroli, G., Smith,G.,Fraser,W.D.,etal. 2018. Effect of High Dose Folic Acid Supplementation in Pregnancy on Pre-Eclampsia (FACT): Double Blind, Phase III, Randomised Controlled, International, Multicentre Trial. BMJ, 362, k3478.
  • Zabri, H,. Kodjo, C., Benie, A., Bekro, J. M., and Bekro, Y. A. 2008. Phytochemical screening and determination of flavonoids in Secamone afzelii (Asclepiadaceae) extracts, African Journal of Pure and Applied Chemistry, 2(8): 80–82.
Year 2022, Volume: 39 Issue: 4, 1150 - 1156, 29.10.2022

Abstract

References

  • Adinma, E. D. 2013. Maternal and perinatal outcome of eclampsia in tertiary health institution in Southeast Nigeria.JMatern Fetal. 26(2):211-4. doi: 10.3109/14767058.2012.722708
  • Ahmed, M., Hwang, J. H., Hasan, M. A., and Han, D. 2018a. Herbal medicine use by pregnant women in Bangladesh: a cross-sectional study. BMC Complement.Altern.Med. 18 (1), 333.doi: 10.1186/s12906-018-2399-y
  • Ahmed, S. M., Nordeng, H., Sundby, J., Aragaw, Y. A., and de Boer, H. J. 2018b.The use of medicinal plants by pregnant women in Africa: A systematic review. J. Ethnopharmacol. 224, 297–313. doi: 10.1016/j.jep.2018.05.032
  • Akbari,S., Khodadadi, B., Ahmadi, S.A.Y., Abbaszadeh, S., Shahsavar,F. Association of VitaminDLeveland Vitamin D Deficiency with Risk of Preeclampsia: A Systematic Review and Updated Meta-Analysis. Taiwan. J. Obstet. Gynecol. 2018, 57, 241–247.
  • Ali, A.M., Alobaid, A., Malhis, T.N., Khattab, A.F. 2019. Effect of Vitamin D3 Supplementation in Pregnancy on Risk of Pre-Eclampsia—Randomized Controlled Trial. Clin.Nutr. 38, 557–563.
  • Al-Ramahi, R., Jaradat, N., and Adawi, D. 2013.Use of herbal medicines during pregnancy in a group of Palestinian women. J. Ethnopharmacol. 150 (1), 79–84. doi: 10.1016/j.jep.2013.07.041
  • Arain, N., Mirza, W.A., Aslam, M. 2015. Review-Vitamin D and the Prevention of Preeclampsia: A Systematic Review. Pak. J. Pharm. Sci. , 28, 1015–1021. [PubM
  • Asuk, A.A and Willie, A. J. (2015. The phytochemical, proximate and mineral compositions of the leaf, stem bark and root of Jatropha curcas. https://doi.org/10.1016/j.apjtb.
  • Cesario, A. 1993. Screening of plants used in Argentine folk medicine for antimicrobial activity. Journal of Ethnopharamacology 139:119-128.
  • Chuang, C. H., Chang, P. J., Hsieh, W. S., Tsai, Y. J., Lin, S. J., and Chen, P. C. (2009. Chinese herbal medicine use in Taiwan during pregnancy and the postpartum period: a population-based cohort study. Int. J. Nurs. Stud. 46 (6), 787–795. doi: 10.1016/j.ijnurstu.2008.12.015
  • Duke, J. and Vasquez, R. 1994. Amazonian Ethnobotanical Dictionary, Florida, CRC Press Incorporated. 122:101-102
  • Eliakim-Ikechukwu, C. F. and Riman, E. B. 2009. The effect of aqueous ethanolic extract of Alchornea cordifolia leaf on the histology of the aorta of Wister rats. Niger J PhysiolSci
  • Felman, A. (2017. Everything you need to know about preeclampsia. Medical news. Feng, M.and DiPetrillo, K. 2009. Non-invasive Blood Pressure Measurement in Mice. Cardiovascular Genomics, 45–55. doi:10.1007/978-1-60761-247-6_3
  • Gharoro, E. P. and Igbafe, A. A. 2000.Pattern of drug useamong antenatal patients in Benin City, Nigeria. Med Sci. Monit. 6(1): 84 - 87.
  • Houghton, P. J., Hylands, P. J., Mensah, A. Y., Hensel, A., and Deters, A. M. 2005. In vitro tests and ethnopharmacological investigations: wound healing as an example,” Journal of Ethnopharmacology, 100(1-2): 100–107.
  • Houghton, P. J., Woldemaraim, T. Z., O’Shea, S. andThyagarajan, S. P. 1996.Two securinega- type alkaloids from phyllanthusamarus.Phytochemistry; 43:715-717
  • Hwang, J. H., Kim, Y.-R., Ahmed, M., Choi, S., Al-Hammadi, N. Q., Widad, N. M.,et al. 2016. Use of complementary and alternative medicine in pregnancy: across-sectional survey on Iraqi women. BMC Complementary Altern.Med. 16,191–191.doi: 10.1186/s12906-016-1167-0
  • Illamola, S. M., Amaeze, O. U., Krepkova, L. V., Birnbaum, A. K., Karanam, A., Job, K. M., et al. 2020. Use of Herbal Medicine by Pregnant Women: WhatPhysicians Need to Know. Front. Pharmacol. 10, 1483–1483. doi: 10.3389/fphar.2019.01483
  • Kafaru, E. 1994. Immense help from nature’s workshop. Nigeria, Elikat Health services Limited. P. 32.
  • Kennedy, D. A., Lupattelli, A., Koren, G., and Nordeng, H. 2013.Herbalmedicine use in pregnancy: results of a multinational study. BMC Complement.Altern.Med. 13, 355.doi: 10.1186/1472-6882-13-355
  • Khadivzadeh, T., and Ghabel, M. 2012.Complementary and alternative medicine use in pregnancy in Mashhad, Iran 2007-8.Iran J. Nurs. Midwifery Res. 17 (4), 263–269.
  • Laelago, T. 2018. “Herbal Medicine Use during Pregnancy: Benefits and Untoward Effects,” in Herbal Medicine. Ed. P. Builders. London: IntechOpen.
  • Mensah, A. Y., Houghton, P. J., Akyirem, G. N. A. et al. 2004. Evaluation of the antioxidant and free radical scavenging properties of Secamone afzelii Rhoem,” Phytotherapy Research, 18(12): 1031-1032, 2004.
  • Mirzakhani, H., Litonjua, A.A., McElrath, T.F., O’Connor, G., Lee-Parritz, A., Iverson, R., Macones, G., Strunk, R.C., Bacharier, L.B., Zeiger, R., et al 2016. Early Pregnancy Vitamin D Status and Risk of Preeclampsia. J. Clin. Investig., 126, 4702–4715.
  • Mol, B.W.J., Roberts, C.T., Thangaratinam, S., Magee, L.A., de Groot, C.J.M., Hofmeyr, G.J. Pre-Eclampsia.Lancet 2016, 387, 999–1011.J. Clin. Med. 2019, 8, 1625 15 of 22
  • Molh, A. K., Ting, L. C., Khan, J., Al-Jashamy, K., Jaafar, H., and Islam, M. N. (2008.Histopathological studies of cardiac lesions after an acute high dose administration of methamphetamine. The Malaysian journal of medical sciences : MJMS, 15(1), 23–30.
  • Nassar, N., Halligan, G.H., Roberts, C.L., Morris, J.M., Ashton, A.W. Systematic Review of First-Trimester VitaminDNormativeLevelsandOutcomesofPregnancy. Am. J.Obstet. Gynecol. 2011,205,e1–e7. [CrossRef] 40. Roth, D.E., Leung, M., Mesfin, E., Qamar, H., Watterworth, J., Papp, E. Vitamin D Supplementation during Pregnancy: State of the Evidence from a Systematic Review of Randomised Trials. BMJ 2017, 35, j5237.
  • Olaleye, M. T., Adegboye, O. O. and Akindahunsi, A. A. 2006.Alchornea cordifoli extract protects Wistar albino rats against acetaminophen-induced liver damage. Afr J Biotech. 5:2439-45
  • Orief, Y. I., Farghaly, N. F., and Ibrahim, M. I. A. 2014.Use of herbal medicines among pregnant women attending family health centers in Alexandria. Middle East Fertility Soc. J. 19 (1), 42–50. doi: 10.1016/j.mefs.2012.02.007
  • Pereira-Junior, P.P., Marocolo, M., Rodrigues, F.P., Medei, M. and Nascimento, J.H.M. 2010. Noninvasive method for electrocardiogram recording in conscious rats: feasibility for heart rate variability analysis. Anais da Academia Brasileira de Ciências 82(2): 431-437
  • Purswani, J.M., Gala, P., Dwarkanath, P., Larkin, H.M., Kurpad, A., Mehta, S. 2017. The Role of Vitamin D in Pre-Eclampsia: A Systematic Review. BMC Pregnancy Childbirth . 17, 231.
  • Rodríguez-García, C., Sanchez-Quesada, C., and Gaforio, J. 2019. Naturally lignin rich food: a dietary tool for health promotion.
  • Saccone, G., Sarno, L., Roman, A., Donadono, V., Maruotti, G.M., Martinelli, P. 2016. 5-Methyl-Tetrahydrofolate in Prevention of Recurrent Preeclampsia. J. Matern. Neonatal Med., 29, 916–920.
  • Segura-Campos, M. R., Peralta-González, F., Castellanos-Ruelas, A., Chel-Guerrero, L. A., andBetancur-Ancona, D. A. 2013. Effect of Jatropha curcas peptide fractions on the angiotensin I-converting enzyme inhibitory activity. BioMed research international, 2013, 541947. https://doi.org/10.1155/2013/541947
  • Sofowora, E. A. 1982. Medicinal plants and traditional medicine in Africa. John Wiley and sons Ltd., Hoboken, 64
  • Stefańska, K., Zieliński, M., Zamkowska, D., Adamski, P., Jassem-Bobowicz, J., Piekarska, K., Jankowiak, M., Leszczyńska, K., Świątkowska-Stodulska, R., Preis, K., Trzonkowski, P., andMarek-Trzonkowska, N. 2020. Comparisons of Dipstick Test, Urine Protein-to-Creatine Ratio, and Total Protein Measurement for the Diagnosis of Preeclampsia. International journal of environmental research and public health, 17(12), 4195. https://doi.org/10.3390/ijerph17124195
  • Ugbogu, O.A. and Chukwuma, E.C. 2019.Ethnobotany of Okomu Forest Reserve, Edo State, Nigeria. J. Appl. Sci. Environ. Manage., 23 (7): 1391-1401
  • Wei, S.-Q., Qi, H.-P., Luo, Z.-C., Fraser, W.D. 2013 Maternal Vitamin D Status and Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis. J. Matern. Fetal. Neonatal Med., 26, 889–899.
  • Wen, S.W., White, R.R., Rybak, N., Gaudet, L.M., Robson, S., Hague, W., Simms-Stewart, D., Carroli, G., Smith,G.,Fraser,W.D.,etal. 2018. Effect of High Dose Folic Acid Supplementation in Pregnancy on Pre-Eclampsia (FACT): Double Blind, Phase III, Randomised Controlled, International, Multicentre Trial. BMJ, 362, k3478.
  • Zabri, H,. Kodjo, C., Benie, A., Bekro, J. M., and Bekro, Y. A. 2008. Phytochemical screening and determination of flavonoids in Secamone afzelii (Asclepiadaceae) extracts, African Journal of Pure and Applied Chemistry, 2(8): 80–82.
There are 40 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Clinical Research
Authors

Kenneth Atoe 0000-0001-7638-6040

Macdonald Idu

Publication Date October 29, 2022
Submission Date September 18, 2021
Acceptance Date October 15, 2021
Published in Issue Year 2022 Volume: 39 Issue: 4

Cite

APA Atoe, K., & Idu, M. (2022). The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats. Journal of Experimental and Clinical Medicine, 39(4), 1150-1156.
AMA Atoe K, Idu M. The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats. J. Exp. Clin. Med. October 2022;39(4):1150-1156.
Chicago Atoe, Kenneth, and Macdonald Idu. “The Effects of Methanolic Plant Extract on the Cardiovascular System of Induced PreeclampticWistar Rats”. Journal of Experimental and Clinical Medicine 39, no. 4 (October 2022): 1150-56.
EndNote Atoe K, Idu M (October 1, 2022) The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats. Journal of Experimental and Clinical Medicine 39 4 1150–1156.
IEEE K. Atoe and M. Idu, “The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats”, J. Exp. Clin. Med., vol. 39, no. 4, pp. 1150–1156, 2022.
ISNAD Atoe, Kenneth - Idu, Macdonald. “The Effects of Methanolic Plant Extract on the Cardiovascular System of Induced PreeclampticWistar Rats”. Journal of Experimental and Clinical Medicine 39/4 (October 2022), 1150-1156.
JAMA Atoe K, Idu M. The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats. J. Exp. Clin. Med. 2022;39:1150–1156.
MLA Atoe, Kenneth and Macdonald Idu. “The Effects of Methanolic Plant Extract on the Cardiovascular System of Induced PreeclampticWistar Rats”. Journal of Experimental and Clinical Medicine, vol. 39, no. 4, 2022, pp. 1150-6.
Vancouver Atoe K, Idu M. The effects of methanolic plant extract on the cardiovascular system of induced preeclampticWistar rats. J. Exp. Clin. Med. 2022;39(4):1150-6.